Uniformly (14)C-ring-labeled 2,4-dichlorophenoxyacetic acid: a metabolism study in bluegill sunfish, Lepomis macrochirus.

The fate of 2,4-dichlorophenoxyacetic acid (2,4-D), a mixture of [phenyl(U)-(14)C]-2,4-D and unlabeled 2,4-D, in bluegill sunfish was investigated after exposure to approximately 11 ppm under static conditions for 4 days. Total radioactive residues (TRR) in whole fish increased from 0.41 ppm on day 1 to 0.60 ppm on day 3. TRR levels in fillet (edible) and viscera (nonedible) of treated fish on day 4 were 0.41 and 1.9 ppm, respectively. Most residues in both matrices were acetonitrile soluble; small amounts were hexane soluble or unextractable with solvents. Acid and base hydrolyses with ethyl acetate partitioning were used to release the fillet unextractable residues. The identification of 2,4-D and 2,4-dichlorophenol (2,4-DCP) in the fillet was conclusively confirmed by GC-MS analysis. On the basis of the experimental data from this study, a metabolic pathway for 2,4-D in bluegill sunfish in which the 2,4-D is metabolized to 2,4-DCP and conjugates of 2,4-D and 2,4-DCP is proposed.

Comparative degradation of [14C]-2,4-dichlorophenoxyacetic acid in wheat and potato after Foliar application and in wheat, radish, lettuce, and apple after soil application.

The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) applied foliarly as the 2-ethylhexyl ester (EHE) to wheat and potatoes, to the soil as the dimethylamine (DMA) salt under apple tree canopies, and preplant as the free acid for wheat, lettuce, and radish was studied to evaluate metabolic pathways. Crop fractions analyzed for (14)C residues included wheat forage, straw, and grain; potato vine and tubers; and apple fruit. The primary metabolic pathway for foliar application in wheat is ester hydrolysis followed by the formation of base-labile 2,4-D conjugates. A less significant pathway for 2,4-D in wheat was ring hydroxylation to give NIH-shift products 2,5-dichloro-4-hydroxyphenoxyacetic acid (4-OH-2,5-D), 4-OH-2,3-D, and 5-OH-2,4-D both free and as acid-labile conjugates. The primary metabolic pathway in potato was again ester hydrolysis. 2,4-D acid was further transformed to 4-chlorophenoxyacetic acid and 4-OH-2,5-D. For the soil applications, (14)C residues in the crops were low, and characterization of the (14)C residues indicated association with or incorporation into the biochemical matrix of the tissue. The degradative pathways observed in wheat are similar to those characterized in other intact plant studies but differ from those in studies in wheat cell suspension culture in that no amino acid conjugates were observed.

Metabolism of 2,4-dichlorophenoxyacetic acid in laying hens and lactating goats.

2,4-Dichlorophenoxyacetic acid (2,4-D) labeled with (14)C was found to be rapidly eliminated by laying hens and lactating goats dosed orally for 7 consecutive days at 18 mg/kg of food intake and for 3 consecutive days at 483 mg/kg of food intake, respectively. Excreta of hens and goats contained >90% of the total dose within 24 h after the final dose. Tissue residues were low and accounted for <0.1% of the dose in these animals. For hens, the residues in muscle, liver, and eggs (0.006-0.030 ppm) were lower than those found in fat and kidney (0.028-0.714 ppm), 2,4-D equivalents. The tissue with highest residue in goat was the kidney at 1.44 ppm, 2,4-D equivalents. Milk, liver, composite fat, and composite muscle had significantly lower residue levels of 0.202, 0.224, 0.088, and 0.037 ppm, respectively. The most abundant tissue residue was 2,4-D and acid/base releasable residues of 2,4-D. A minor metabolite was identified as 2,4-dichlorophenol.

Three histopathological types of retinoblastoma and their relation to heredity and age of enucleation.

The histopathology of 61 eyes was studied with special attention to the morphology of the retina adjacent to the main tumour. Three retinal types were distinguished. Retina type 1 (RT-1, 28 specimens) contained a single tumour that was sharply demarcated from surrounding normal retina. In retina type 2 (RT-2, 29 specimens) large parts of the retina were affected and the main tumour mass gradually blended with the adjacent pathological retina. Retina type 3 (RT-3, four specimens) was characterised by a retina almost entirely affected by diffuse tumour growth. RT-1 correlated significantly with early enucleation (0-3 years) both in hereditary and non-hereditary cases. RT-2 was seen in eyes enucleated later (2-5 years). The progressing tumour may release growth factors in the intraocular space that stimulate the cells of the adjacent retina and lead to multiple new primary tumours in the adjacent retinal area. RT-3 was only present in non-hereditary cases with late enucleation (at 2-5 years). Hereditary retinoblastoma cases are usually detected early. Therefore in hereditary cases RT-1 is significantly more common than RT-2. In 25 eyes of the 44 patients with unilateral sporadic retinoblastoma, multifocal tumours of the retina were observed. Such cases should not mistakenly be classified as hereditary cases on the basis of the histological pattern of multifocality of the tumour process.

[Pseudoretinoblastoma. Differential diagnosis of retinoblastoma]. / Pseudoretinoblastom. Differentialdiagnostik des Retinoblastoms.

Between 1958 and 1988, at the ophthalmopathological laboratory of Utrecht University, different diseases were found in 60 eyes of 59 patients with the clinically established or tentative diagnosis of retinoblastoma. In this collection of extremely heterogeneous cases of pseudoretinoblastoma congenital malformations accounted for around 50% of the cases, inflammatory conditions for 35% and other diseases, including other tumors, for 15%. Modern examination and treatment methods have brought about a considerable reduction in the number of such cases.

Delayed lens-induced inflammation.

Of a 61-year-old woman with bilateral high myopia and bilateral juvenile cataract (which had been operated upon over 40 years ago), the blind and painful left eye was removed because of a tumour-like mass protruding from the pupil into the anterior chamber. Histological examination revealed this mass to be an anteriorly subluxated lens remnant with the posterior side touching the anterior face of the iris. Exclusively in this area of contact there was a typical lens-induced inflammatory reaction. We assume that this reaction could occur only because of the presence of vascular tissue, i.e. the iris stroma. Immunopathological considerations would seem to make this plausible.

Aphakia versus pseudophakia. A clinico-pathological study.

Eighteen enucleated pseudophakic and 14 aphakic eyes were histopathologically described. An analysis was made of the histologic data in combination with clinical information. In conclusion, cataract extraction with subsequent implantation of an artificial lens seems to bear a higher risk than cataract extraction alone, notwithstanding-perhaps--better technical work during implant surgery. The presence of an intraocular lens may induce either fatal inflammations or complications necessitating other surgical interventions, which may contribute to a fatal outcome. However the proportion of enucleated eyes to the total number of lens implantations is almost negligible, it probably reflects the clinical complications.

[Retinoblastoma--clinical diagnostic errors]. / Retinoblastom--klinische fehldiagnosen.

The author discusses clinical and histological findings in 6 patients whose complaints had been wrongly diagnosed, out of 91 patients in whom a retinoblastoma had been diagnosed at the ophthalmo-pathological laboratory of the University Eye hospital in Utrecht between 1960 and 1981. In 6 other cases the diagnosis was doubtful. All the cases occurred before 1974. The faulty diagnoses were: spontaneously necrotized retinoblastoma, congenital anomaly, retinal detachment, infection with toxocara canis, sarcoidosis, and angiomatosis retinae. Three patients are still living. If the diagnosis is not certain a blind eye should be removed without delay.

Characterization of some glycolytic enzymes from human retina and retinoblastoma.

GLycolytic enzymes were studied from normal human retinas (both fetal and adult) and from retinoblastomas of eight patients and an established retinoblastoma cell line. No significant differences were found between the enzyme activities in the tissues investigated except for hexokinase and pyruvate kinase, which were significantly decreased in the tumor cells. In fetal retina, five different forms of pyruvate kinase could be detected by electrophoresis (K4, K3M, K2M2, KM3, and M4). In adult retina the K4 isozyme is almost absent, while in retinoblastoma the M4 isozyme is hardly present. In the retinoblastoma cell line, the M4 isozyme is completely absent. Alanine inhibition of pyruvate kinase from the retinoblastoma cell line is more inhibited compared to the pyruvate kinase of fetal retina and retinoblastoma and is even more inhibited compared to adult retina. Electrophoresis of aldolase from adult retina revealed the presence of all potential A-C hybrids (A4, A3C, A2C2, AC3, and C4). Fetal retina, however, is characterized by the predominance of the A type. The same patterns were observed in the retinoblastoma cell line and retinoblastoma. However, in other brain tumors, e.g., gliomas of adults, a five-membered A-C hybrid set is found. Electrophoresis of hexokinase from normal fetal and adult retina revealed the predominance of hexokinase type I; retinoblastoma and retinoblastoma cell line are both characterized by the presence of considerable amounts of hexokinase type II. The isozyme shifts in retinoblastoma result in an enzyme pattern identical to that of fetal retina except for the presence of hexokinase type II.

Amoebic keratitis.

A 67-year-old man with chronic keratitis was treated with a multitude of antibiotics, corticosteroids and other medicines. Despite temporary relief, perforation with iris prolapse occurred about 4 months after the initial symptoms, and the eye had to be removed. Histological examination revealed cystic bodies in the corneal stroma which could be identified as belonging to the genus Acanthamoeba. Trophozoites were seen as well. Although these amoebae are free-living organisms, occurring almost everywhere in the water and air, corneal infections are rare and have been reported only recently. It has been suggested that Acanthamoebae may only invade the tissues in the case of mixed infections or in corneas with a reduced immunological response, e.g. after corticosteroid therapy. Conservative therapy seems to have little effect, although antibiotic/antiviral/antimycotic treatment should supplement antiamoebic therapy, considering the possibility of mixed infections. Penetrating keratoplasty was indicated in most of the reported cases and usually had a beneficial effect.

Medulloepithelioma arising from the posterior pole.

In the right eye of a 2 1/2-year-old boy a markedly prominent tumor, arising from the posterior pole, was found. The clinical diagnosis was retinoblastoma and the eye was removed. Histologically, however, this appeared to be a medulloepithelioma originating in the optic disc and in the posterior retina: an extremely rare localization as these tumors usually originate in the ciliary region. The tumor mainly consisted of neuroectodermal elements in several degrees of differentiation giving the aspect of a benign (hamartomatous) embryonal brain tumor rather than those of a retinal tumor. Some aspects of the nomenclature are discussed.

[Fatal complications following the implantation of artificial lense (author's transl)]. / Schwere Komplikationen nach Implantation von Kunststofflinsen.

The number of cataract operations with implantation of artificial lenses has been increasing in recent years. However, there is hardly any information available concerning possible serious consequences. While there are detailed reports on histopathological findings following conventional cataract operations, fatal complications of this technically complex intervention are only mentioned occasionally. There were 9 cases with serious complications in our polyclinic in 1976, and this report deals with the histopathological findings in 6 enucleated eyes. The authors warn against ill-considered decisions to perform a lens implantation.

Sweat gland tumour of the eyelid with conjunctival involvement.

An 87-year-old woman presented with a rapidly growing tumour at the nasal side of the upper eyelid. The clinical diagnosis was basal cell carcinoma. During surgery, the impression of malignancy was accentuated by the finding that even the conjunctiva had been invaded. Histological examination revealed an eccrine acrospiroma with, indeed, many mitoses but, on the other hand, a completely benign aspect. Besides, there was no recurrence after 1 year.

Human cord blood lymphocytes. Ultrastructural and immunologic surface marker characteristics; a comparison with B- and T-cell lymphomas.

The ultrastructural and surface marker characteristics of human cord blood lymphocytes were studied. These properties were compared with those in cells of patients in the leukemic phase of both malignant lymphoma, poorly differentiated lymphocytic type, and mycosis fungoides. Nuclear folding in cord blood lymphocytes was similar to that seen in lymphocytes of patients with malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides. Surface marker characteristics of cord blood lymphocytes included increased percentages of surface IgD on cells bearing surface immunoglobulins and decreased percentages of E-rosette-forming cells. The hypothesis that both malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides represent an arrest in the normal lymphocyte maturation sequence is discussed.

[Juvenile xanthogranuloma of the uvea in an adult]. / Juveniles Xanthogranuloma uveae bei einem Erwachsenen

Because of a quick growing iris tumor right eye was enucleated in a man 22 years old. It seemed to be malignant according to fluorescein angiography and isotope examinations. On histopathological examination only a juvenile xantogranuloma was found, a benign granulation process of unknown etiology, occurring mainly in young children, where corresponding skin changes could also be found. The 'tumor' is composed mainly by histiocytes sometimes also numerous giant cells and it has numerous fine vessels which can give rise to a spontaneous hyphaema--a clinically important feature. A secondary glaucoma may subsequently occur. An early diagnosis is essential because these granulation tissues are very sensitive to X-rays. Unfortunately the correct diagnosis is often made only histologically, whereas the clinical signs imitate a malignant process. One can not rely here on isotope examinations. Flourescein angiography may lead to the correct diagnosis but only in very experienced hands.